The design, synthesis, and evaluation of ligands which interact specifically with particular CNS receptors are essential for the elucidation of the function and mechanism of action of these receptors. Phencyclidine binding sites have been implicated as allosteric sites within an ion channel which interact with glutamate receptors of the N-methyl-D-aspartate (NMDA) type. NMDA, an excitatory amino acid, acts to open these ion channels. Some phencyclidine (PCP)-like compounds have recently been reported to exert a protective effect against neuronal degeneration in ischemia; they supposedly act as antagonists against the depolarizing action of NMDA in animal brain. Studies are in progress towards the design and synthesis of new phencyclidine-like compounds which might exert protection against neuronal degeneration, and others for their anticonvulsant (anti-epileptic) effects. One of our affinity ligands for the PCP site, metaphit, has been used to study the function of the PCP site and its interaction with the excitatory amino acids. The design and synthesis of new affinity ligands for the phencyclidine receptor is in progress. Also, the affinity of various opioids for their receptors, their pharmacological study in a number of assays, as well as the pharmacological evaluation of compounds from the stimulant and depressant classes of CNS agents, has been studied under the auspices of the Committee on Problems of Drug Dependence with the goal of identifying new ligands which interact with specific receptors as agonists or antagonists, with fewer undesirable side-effects in vivo. Data from these studies have been utilized by the Expert Committee of the World Health Organization concerned with the evaluation of scientific data used for drug scheduling under the Psychotropic Substances Convention.